https:\/\/doi.org\/10.1002\/cbic.202400497<\/a><\/p>\n\n\n\nGraphical Abstract<\/h2>\n\n\n\n M at work: PsiM is the methyltransferase that completes psilocybin biosynthesis in magic mushrooms. Crystal structures and kinetic analyses of the wild type enzyme and two engineered variants provided profound insight into why the residue Asn247 is key for PsiM’s capability to dimethylate.<\/p>\n\n\n\nThe Psilocybe cubensis<\/em> SAM-dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved from monomethylating RNA methyltransferases, PsiM acquired a key amino acid exchange in the secondary sphere of the active site, M247\u2005N, which is responsible for its capacity to dimethylate. Two variants, PsiMN247M<\/sup> and PsiMN247A<\/sup>, were generated to further examine the role of Asn247 for mono- and dimethylation in PsiM. Our structural and kinetic analyses of the variants suggest that Asn247 is essential to allow enough space in the active site for multiple methylations while also participating in a network of hydrogen bonds that stabilizes secondary structure elements in the immediate vicinity of the active site for optimal methylation of norbaeocystin.<\/p>\n","protected":false},"excerpt":{"rendered":"The Second Methylation in Psilocybin Biosynthesis Is Enabled by a Hydrogen Bonding Network Extending into the Secondary Sphere Surrounding the Methyltransferase Active Site Jesse Hudspeth, Kai Rogge, Tobias Wagner, Maximilian M\u00fcll, Dirk Hoffmeister, Bernhard Rupp, Sebastiaan Werten First published: 16 October 2024 https:\/\/doi.org\/10.1002\/cbic.202400497 Graphical Abstract M at work: PsiM is the methyltransferase that completes psilocybin biosynthesis in magic mushrooms. Crystal structures […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-235","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=\/wp\/v2\/posts\/235","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=235"}],"version-history":[{"count":4,"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=\/wp\/v2\/posts\/235\/revisions"}],"predecessor-version":[{"id":240,"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=\/wp\/v2\/posts\/235\/revisions\/240"}],"wp:attachment":[{"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=235"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=235"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ruppweb.org\/psilosophy\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=235"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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